These studies are directed towards the development of rational and effective therapy of ocular fungal infections. The standard model of corneal infection with Candida species in the rabbit eye will be used to evaluate single and combined therapy. Further development of this model is planned using other filamentous fungi, and topical therapy and subconjunctival therapy will be used and the response evaluated. Additives and synergistic/antagonistic effects will be noted. The effect of corticosteroid on clinical recovery and isolate recovery rate will be evaluated. The previously described model will be used to develop models of filamentous fungus infection, particularly Fusarium and Aspergillus and similar studies with drugs will then take place. A bioassay technique for evaluating imidazole levels in aqueous and solid tissue, such as cornea, will be used to correlate drug levels with clinical response. In the rat eye bioassay studies we will evaluate the intraocular penetration following systemic administration. The development of a rat endogenous model of filamentous ocular disease is planned to evaluate the pathogenesis of fungal invasion of intraocular structures. Studies of neonatal fungal infection will help to define the period of susceptibility following birth in these animals. An in vitro model of ocular toxicity has been developed using excised ciliary body in tissue culture medium. Various chemotherapeutic agents, organisms and cell-free filtrates from ocular pathogens will be studied for their effect on these anatomic structures. Such data will be helpful in arriving at toxic levels of therapeutic agents and may define the role and risks of intraocular therapy by antifungal agents. The addition of cell-free filtrates from fungal cultures may help to define the role of fungal metabolites in causing intraocular tissue damage.